7.13B: Annotating Genomes

Genome annotation is the identification and understanding of the genetic elements of a sequenced genome.

LEARNING OBJECTIVES

Define genome annotation

Key Takeaways

Genome projects are scientific endeavors that ultimately aim to determine the complete genome sequence of an organism (be it an animal, a plant, a fungus, a bacterium, an archaean, a protist, or a virus). They annotate protein-coding genes and other important genome-encoded features. The genome sequence of an organism includes the collective DNA sequences of each chromosome in the organism. For a bacterium containing a single chromosome, a genome project will aim to map the sequence of that chromosome.

Once a genome is sequenced, it needs to be annotated to make sense of it. An annotation (irrespective of the context) is a note added by way of explanation or commentary. Since the 1980’s, molecular biology and bioinformatics have created the need for DNA annotation. DNA annotation or genome annotation is the process of identifying the locations of genes and all of the coding regions in a genome and determining what those genes do.

Figure: Genome Annotation: Here a small region of genome is annotated, with various elements identified. The annotation of an entire genome would entail a similar in depth analysis of thousand even millions of such DNA sequences.

Genome annotation is the process of attaching biological information to sequences. It consists of two main steps: identifying elements on the genome, a process called gene prediction, and attaching biological information to these elements. Automatic annotation tools try to perform all of this by computer analysis, as opposed to manual annotation (a.k.a. curation) which involves human expertise. Ideally, these approaches co-exist and complement each other in the same annotation pipeline (process). The basic level of annotation is using BLAST for finding similarities, and then annotating genomes based on that. However, nowadays more and more additional information is added to the annotation platform. The additional information allows manual annotators to deconvolute discrepancies between genes that are given the same annotation. Some databases use genome context information, similarity scores, experimental data, and integrations of other resources to provide genome annotations through their Subsystems approach. Other databases rely on both curated data sources as well as a range of different software tools in their automated genome annotation pipeline.

Structural annotation consists of the identification of genomic elements: ORFs and their localization, gene structure, coding regions, and the location of regulatory motifs. Functional annotation consists of attaching biological information to genomic elements: biochemical function, biological function, involved regulation and interactions, and expression.

These steps may involve both biological experiments and in silico analysis. Proteogenomics based approaches utilize information from expressed proteins, often derived from mass spectrometry, to improve genomics annotations. A variety of software tools have been developed to permit scientists to view and share genome annotations. Genome annotation is the next major challenge for the Human Genome Project, now that the genome sequences of human and several model organisms are largely complete. Identifying the locations of genes and other genetic control elements is often described as defining the biological “parts list” for the assembly and normal operation of an organism. Scientists are still at an early stage in the process of delineating this parts list and in understanding how all the parts “fit together. ”

Key Points

• Once a genome is sequenced, all of the sequencings must be analyzed to understand what they mean.
• Critical to annotation is the identification of the genes in a genome, the structure of the genes, and the proteins they encode.
• Once a genome is annotated, further work is done to understand how all the annotated regions interact with each other.

Key Terms

• BLAST: In bioinformatics, Basic Local Alignment Search Tool, or BLAST, is an algorithm for comparing primary biological sequence information, such as the amino-acid sequences of different proteins or the nucleotides of DNA sequences.
• in silico: In computer simulation or in virtual reality